Studies on the "genetics and pathogenesis of bluetongue virus" will make use of wild type (WT) and vaccine (V) strains of the four serotypes (10, 11, 13, and 17) of bluetongue virus (BTV) present in the United States. These studies will make use of a genetic approach to study basic features of BTV biology and pathogenesis and will focus on four main areas: (i) Analysis of the genome RNA of WT and V strains of BTV by electrophoresis and oligonucleotide fingerprinting. The experiments will identify serotype-specific and vaccine-specific markers in the genome structure investigate the degree of heterogeneity present in the V strain populations of each serotype, and enumerate and locate the sites of mutations in the V strains. (ii) Analysis of the proteins synthesized by WT and V strains of BTV by electrophoresis and immunoblotting. These studies will identify serotype-specific and vaccine-specific markers for individual protein species and investigate the immunologic relationships between serotypes and between WT and V strains at the level of individual protein species. (iii) Genetic analysis of the genome segment reassortment potential of WT and V strains of BTV. Specifically, these experiments will examine the potential of V strains to reassort genome segments and the potential of field strains of virus to rescue the serotypic antigens of a V strain by reassortment. (iv) Analysis of the pathogenic potential of BTV reassortants. A mouse model for pathogenesis will be used to determine if reassortants derived from V strains can be pathogenic, thereby indicating that the V strains are genetically unstable if used as a polyvalent vaccine. The pathogenic potential of reassortants, in which WT has rescued the serotypic antigens of a V strain, will be analyzed to determine the possibility of genetic interaction between V strains and field strains resulting in pathogenic reassortants having the serotypic specificity of the V strain. Specific BTV genes involved in pathogenesis will be identified and maps establishing the coding relationships between genome segments and specific protein species will be generated for each of the four BTV serotypes. These experiments will provide significant new information on the genetics and pathogenesis of BTV. In addition, they will provide information important in devising vaccine strategies for important human pathogens (e.g., rotaviruses). The answers to these questions are critical to any strategy making use of a polyvalent attenuated vaccine for control of viruses with segmented genomes.